The unique ureotelic tilapia Alcolapia grahami lives in the highly alkaline and saline waters of Lake Magadi, Kenya (pH ~10.0, alkalinity ~380 mmol·L1, Na+~350 mmol·L1, Cl~110 mmol·L1, osmolality ~580 mosmol·kg1). In 100% lake water, the Magadi tilapia maintained plasma Na+, Cl, and osmolality at levels typical of marine teleosts and drank the medium at 8.01 ± 1.29 mL·kg1·h1. Gill chloride cells were predominantly of the sea water type (recessed, with apical pits) but a few freshwater-type chloride cells (surficial, with flat apical exposure) were also present. Whole-body Na+and Clconcentrations were relatively high and exhibited larger relative changes in response to salinity transfers than did plasma ions. All fish succumbed upon acute transfer to 1% lake water, but tolerated acute transfer to 10% lake water well, and gradual long-term acclimation to both 10 and 1% lake water without change in plasma cortisol. Plasma osmolytes were here maintained at levels typical of freshwater teleosts. Curiously, drinking continued at the same rate in fish adapted to 1% lake water, but chloride cells were now exclusively of the freshwater type. Significant mortality and elevated cortisol occurred after acute transfer to 200% lake water. However, the fish survived well during gradual adaptation to 200% lake water, although plasma cortisol remained chronically elevated. Urea levels accounted for only 23% of internal osmolality in 100% lake water but responded to a greater extent than plasma ions during exposure to 10 and 200% lake water, decreasing by 2842% in the former and increasing by over 500% in the latter relative to simultaneous-control values. Urea thereby played a small but significant role (up to 8% of internal osmolality) in osmoregulation.